Method for preparing solid delivery system for encapsulated...

Drug – bio-affecting and body treating compositions – Preparations characterized by special physical form – Food or edible as carrier for pharmaceutical

Reexamination Certificate

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C424S441000, C424S464000, C424S465000, C514S778000, C514S781000, C514S783000, C514S951000

Reexamination Certificate

active

06541025

ABSTRACT:

FIELD OF THE INVENTION
Background of the Invention
It is known by those skilled in the art that orally administering pharmaceuticals to animals, specifically cats, dogs and horses, can be exceedingly difficult. The animal may reject the entire dose, or parts of the dose, leaving the vet or the owner frustrated in trying to administer the proper amount.
The true test of a delivery system for animals is whether the pharmaceutical is successfully administered repeatedly. As is often the case, when treating an illness or even a permanent condition of an animal, doses are repeated daily or even several times a day. Once an animal has tasted the unpalatable pharmaceutical that the vet or owner has attempted to hide or disguise, it becomes uncooperative when the administration is repeated. Applicants have discovered a delivery system that presents the pharmaceutical in a palatable form such that the drug can be successfully and easily administered repeatedly.
Heretofore, attempts to alleviate the problem of administering pharmaceuticals have been made a number of ways, including hiding the drug in food. Usually the keen smell of the animal will allow it to detect and reject the pharmaceutical hidden therein. The taste and smell of pharmaceuticals can be masked through the use of flavorings and/or masking agents. Typically, this is only partially successful, as the taste and smell are not completely eliminated.
The pharmaceutical may be microencapsulated, and administered in a gel capsule, but the animal will usually chew the capsule, rupture it, taste the unpalatable pharmaceutical and reject it. Future administrations of the encapsulated pharmaceuticals are thwarted. The use of gel capsules has the additional disadvantages of being costly for delivering large doses of pharmaceuticals. The microencapsulated pharmaceutical may be tabletted using a conventional tablet press. However, such a process invariably damages or ruptures the capsules, defeating the benefits of encapsulation.
The present invention is an oral delivery system, wherein the system delivers microencapsulated pharmaceuticals, wherein the microencapsulation is intact and the pharmaceutical is delivered in a palatable form. Further, the present invention provides the pharmaceutical in a low cost, concentrated form that is easily administered. The delivery system comprises at least one lipid, dry particles including at least one pharmaceutical and at least one filler, and a surfactant, wherein the dry particles are continuously coated by the lipid and form a suspension with the lipid. The suspension exhibits thixotropic or pseudoplastic flow properties. The fillers include cellulose, starch and whey, and comprise from about 60 to 80% of the system (all percentages stated herein are weight percent, unless otherwise indicated). Optionally, flavorings can be added to the dry particles and include cheese, butter, cream, and egg flavorings. Optionally, the pharmaceutical can comprise all of the dry particles, and serve as filler as well as pharmaceutical.
The process for preparing the present delivery system comprises melting the lipid and mixing with the surfactant, blending the dry particles which include the pharmaceutical, filler and, optionally, flavorings with the melted lipid, and pouring or molding the suspension to provide the dose.
U.S. Pat. No. 4,327,076 discloses a compressed chewable antacid tablet which contains from about 10 to 50% active ingredient, from about 2 to 45% fat, from about 25 to 75% fat-sorbing materials, such as starch, and from about 20 to 60% tablet bonders, such as sugars, and surfactants and flavors. The process disclosed by U.S. Pat. No. 4,327,076 involves a pretreatment step wherein the fat is melted and is mixed with fat-sorbing material, tablet bonders and flavorings, forming a fatty powder. The second step involves mixing the active ingredient and surfactant with the pretreated fat and forming a free flowing powder wherein each active ingredient particle is coated with the pretreated fat. The powder thus produced is compressed into chewable pellets.
The above patent fails to disclose the claimed delivery system, wherein the pellets are not compressed into tablets but molded or poured.
U.S. Pat. No. 4,581,381 discloses a chewable antacid pill or pellet containing solid antacid particles having a particle size under 100 millimicrons coated with a fatty material, a surfactant, and a flavoring. The pill or pellet is formed by molding and provides a non-chalky, non-gritty pellet. The antacid particles are coated by melting the fatty material and mixing in the surfactant, the antacid and the flavorings.
The above patent requires very small particles (100 millimicrons), which are not required in the present process.
Neither of the above-referenced patents disclosed the present invention as disclosed and claimed herein.
SUMMARY OF THE INVENTION
The present invention comprises an oral delivery system comprising at least one lipid, at least one surfactant, dry particles including at least one pharmaceutical, and at least one filler, wherein the dry particles are continuously coated by the lipid and form a homogeneous suspension with the lipid. The suspension exhibits thixotropic and/or pseudoplastic properties. The suspension is formed into the desired dose by molding or pouring the suspension when in a liquid or semi-liquid state.
DETAILED DESCRIPTION OF THE INVENTION
The lipids of the present invention may be of animal, vegetable or mineral origin, which are substantially water-insoluble, inert, non-toxic hydrocarbon fats and oils and derivatives thereof, and may comprise any of the commonly commercially available fats or oils approved by the Food & Drug Administration, having melting points in the range of about 90 to 160° F. The lipid may comprise a vegetable oil base commonly known as hard butter. Hard butters are hydrogenated, press fractionated or other processed oils that are processed or recombined to have a solid fat index (percent solid fat vs. temperature) similar to that of cocoa butter. However, other lipids may be used that are relatively hard or solid at room temperature, but melt rapidly in the mouth at a temperature of about 98° F. (mouth temperature). The lipid is employed in the amounts within the range of from about 20 to 40%. Above about 40%, the suspension flows too readily and does not exhibit thixotropic or pseudoplastic flow properties. When present below about 20%, the amount of lipid is not sufficient to completely coat the dry particles.
Examples of suitable lipids include tallow, hydrogenated tallow, hydrogenated vegetable oil, almond oil, coconut oil, corn oil, cottonseed oil, light liquid petrolatum, heavy liquid petrolatum, olein, olive oil, palm oil, peanut oil, persic oil, sesame oil, soybean oil or safflower oil. Additionally, stearines can be used as a lipid in the present invention. The addition of stearines to the product provides the favorable property of mold-release. Further, the addition of stearines raises the melting point of the composition as high as about 100° F., which is particularly beneficial when the product is shipped or stored in unrefridgerated compartments.
The fillers of the present invention are pharmacologically inert and optionally nutritionally beneficial to humans and animals. Such fillers include cellulose such as microcrystalline cellulose, grain starches such as cornstarch, tapioca, dextrin, sugars and sugar alcohols such as sucrose sorbitol, xylitol, mannitol and the like. Preferred fillers include non-fat milk powder, whey, grain brans such as oat bran, and fruit and vegetable pulps. Preferred fillers are finely divided and have a preferred average particle size in the range of about 10 to 500 microns. The fillers are present in the drug delivery device in a concentration of about 60 to 80%. Optionally, the pharmaceutical particles can also serve as filler in the delivery system.
Any emulsifier or surfactant approved for use in foods by the Food and Drug Administration and having a relatively low HLB value, in the range of about 1

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